Insmed Provides Update on iPlex Pivotal Trial Data in Severe Primary IGF-1 Deficiency

Insmed Incorporated (NASDAQ: INSM) provided an update onits ongoing pivotal clinical trial of iPlex(TM) (rhIGF-1/rhIGFBP-3)(Mecasermin rinfibate) for the treatment of children with growthfailure who suffer from Severe Primary IGF-1 (insulin-like growthfactor-1) deficiency (Primary IGFD). Some of these data were recentlyfeatured in a podium presentation at the European Society of PediatricEndocrinology/Lawson Wilkins Pediatric Endocrine Society's 7th JointMeeting. The data demonstrated that as a once-daily IGF-1 therapy,iPlex safely and significantly increased height velocity, the primaryendpoint of the study, in children with short stature due to SeverePrimary IGF-1 deficiency.

Cecelia Camacho-Hubner, M.D., of St. Bartholemew's Hospital,London, United Kingdom commented, "Treatment with twice dailyinjections of rhIGF-I and once-daily injections of rhIGF-I/rhIGFBP-3complex are effective in promoting linear growth in children withSevere Primary IGF-1 deficiency. Patients with Severe Primary IGF-1deficiency are susceptible to spontaneous hypoglycemia; therefore itis important to monitor blood glucose levels before initiating anyhormonal treatment. It is our opinion that the complex hasdemonstrated a superior safety profile in children with Severe PrimaryIGF-1 deficiency, especially regarding the number of hypoglycemicevents and the severity of those events. This is most likely due tothe modulating effects of IGFBP-3. Once a day injections withrhIGF-I/rhIGFBP-3 has been associated with very good compliance in ourpatients".

Data Summary:

Efficacy-

-- All patients were pre-pubertal and identified as having Severe Primary IGF-1 deficiency (including subjects with GH receptor deficiency and GH gene deletion). The patients were characterized with severe short stature, low blood levels of IGF-1, and normal to elevated growth hormone levels.

-- All patients received once-daily injections of iPlex at doses of 0.5 - 2.0 mg/kg, with the goal of restoring and maintaining IGF-1 blood levels in the normal range.

-- 25 of the initial 29 patients enrolled in the study were evaluated for the primary efficacy endpoint: change in annualized height velocity (growth rate) after 6 months of treatment. Additional analyses were performed looking at longer-term treatment.

-- The average pre-treatment height velocity in these 25 children was 3.0 centimeters per year (1.2 inches per year). Increases in height velocity during treatment were related to both the iPlex dose received and the IGF-1 blood levels achieved. In a subset of patients (n=16) treated at a low fixed dose (up to 1.0 mg/kg), a better height velocity was observed in those whose IGF-1 blood levels reached a normal target range than in those with persistently low IGF-1 levels on this dose (8.3 vs 5.6 cm/yr at Month 12, respectively). The overall increase in height velocity in this subset of patients was highly statistically significant (p<0.0001).

-- The importance of adjusting dose to optimize IGF-1 blood levels was demonstrated in the second subset of patients (n=9), whose dose was increased up to 2.0 mg/kg based on IGF-1 levels and clinical outcome. The average 9-month annualized height velocity in this group was 8.2 cm/yr, a 6.0 cm/yr increase over their average pre-treatment height velocity of 2.2 cm/yr (p<0.0001).

-- Since iPlex therapy includes the important binding protein IGFBP-3, which is administered with the IGF-1 in a stable complex of the 2 recombinant proteins, the baseline IGFBP-3 levels were not a consideration when dosing the patients.

Safety

-- Once daily administration of up to 2.0 mg/kg of iPlex was found to safe and well tolerated.

-- Low blood sugar (hypoglycemia) can occur due to the insulin-like effects of IGF-1. However, the frequency of severe hypoglycemia in this iPlex study appeared to be less frequent than that reported in published studies of free rhIGF-1 therapies. No hypoglycemic convulsions or cases of facial nerve paralysis occurred in the iPlex study, both of which are serious adverse events that have been associated with free IGF-1 therapies in published studies.

-- As with all protein products, a proportion of patients developed antibodies to the product. After extensive testing, there was no evidence that the antibodies resulted in neutralization of biologic activity, such as reduced height velocity, nor adverse drug reactions or physical findings.

-- A matched safety comparison was performed of this study with a similar, prospectively-designed, published clinical study of free rhIGF-1 (manufactured by Pharmacia Inc.) in children with Severe Primary IGF-1 deficiency . A two-fold higher incidence of serious adverse events (SAE's) occurred in the free IGF-1 study as compared with the SomatoKine study over a similar time frame.

About Severe Primary IGF-1 deficiency

Severe Primary IGF-1 deficiency encompasses a variety of geneticand acquired conditions in which the action of growth hormone (GH) isabsent or severely attenuated, resulting in low serum levels of IGF-1.Because IGF-1 is the primary mediator of the growth-promoting actionsof GH, SomatoKine replacement therapy in children with Severe PrimaryIGF-1 deficiency is intended to bypass the blocked actions of GH byreplacing the deficient IGF-1, resulting in improved growth.

More on iPlex

Insmed's iPlex is a proprietary drug product for the delivery ofrecombinant insulin-like growth factor I (IGF-1). It is administeredas a preformed complex with a recombinant form of its natural bindingprotein, insulin-like growth factor binding protein 3 (rhIGFBP-3). Thenovel compound is administered as a once-daily subcutaneous injection,which can restore and maintain IGF-1 levels to physiologicallyrelevant levels. The binding protein (rhIGFBP-3) extends the residencetime of IGF-1 in the blood, conferring a superior pharmacokineticprofile as compared with rhIGF-1 alone. In the bound state, the IGF-1is inactive, and remains so until delivered to target tissues in thebody where it is released and becomes biologically active. Thisreduces the risk of short- and long-term safety concerns that havebeen associated with unrestrained levels of free IGF-1.

iPlex has been investigated in a number of other indications inaddition to growth disorders. In patients with Type 1 and Type 2diabetes, administration of iPlex demonstrated a significantimprovement in blood sugar control and a significant reduction indaily insulin use. In children and adults suffering severe burninjury, administration of iPlex demonstrated a significant improvementin muscle protein synthesis and a significant reduction in theinflammatory response associated with the trauma. In elderlyindividuals recovering from hip fractures, administration of iPlexdemonstrated a significant improvement in functional recovery and bonemineral density. In addition to the Severe Primary IGF-1 deficiencyprogram, iPlex is currently being studied in a Phase II clinical trialat the University of California, San Francisco in patients withHIV-Associated Lipodystrophy, and in a Phase II clinical trial at theUniversity of Cambridge, U.K., in patients with Extreme InsulinResistance.

About Insmed

Insmed is a biopharmaceutical company focused on the discovery anddevelopment of drug candidates for the treatment of metabolic diseasesand endocrine disorders. For more information, please visitwww.insmed.com.

Statements included within this press release, which are nothistorical in nature, may constitute forward-looking statements forpurposes of the safe harbor provided by the Private SecuritiesLitigation Reform Act of 1995. Forward-looking statements in thispress release include, but are not limited to, statements regardingclinical trials and goals, our regulatory and business strategies andgrowth opportunities for existing or proposed products. Suchforward-looking statements are subject to numerous risks anduncertainties, including risks that product candidates may fail in theclinic or may not be successfully marketed or manufactured, thecompany may lack financial resources to complete development ofproduct candidates, the FDA may interpret the results of our studiesdifferently than we have, competing products may be more successful,demand for new pharmaceutical products may decrease, thebiopharmaceutical industry may experience negative market trends andother risks detailed from time to time in the company's filings withthe Securities and Exchange Commission. As a result of these and otherrisks and uncertainties, actual results may differ materially fromthose described in this press release. For further information withrespect to factors that could cause actual results to differ fromexpectations, reference is made to reports filed by the Company withthe Securities and Exchange Commission under the Securities ExchangeAct of 1934, as amended. The forward-looking statements made in thisrelease are made only as of the date hereof and Insmed disclaims anyintention or responsibility for updating predictions or financialguidance contained in this release.